Abstract

17β‐estradiol is a steroid hormone that promotes cell survival and prevents from apoptosis in a great variety of tissues. Previous investigations with the murine skeletal muscle C2C12 cell line demonstrated that the action of 17β‐estradiol involves stimulation of PI3K‐Akt. Studies with other cell types have shown that upon its activation Akt can inhibit apoptosis by alternative mechanisms. In this report, we investigated whether the antiapoptotic effect of estrogen in muscle cells is mediated by Akt through interaction and dephosphorylation at Thr 845 of ASK‐1, a MAPKKK pro‐apoptotic protein. When proliferating C2C12 cells were treated with 17β‐estradiol (10−8 M), phosphorylation of ASK1 (Thr 845) and JNK was decreased. However, no significant changes occurred in ASK1 and JNK 1/2 protein levels. On the other hand, treatment with the apoptic agent H2O2 caused a sustained (30 min ‐ 24 h) increase in ASK1 levels and phosphorylation at Thr 845 (associated to stimulation of kinase activity) and, in addition, of JNK 1/2 phosphorylation. Furthermore, a 17β‐estradiol‐dependent interaction between p‐Akt and ASK1 was detected by coimmunoprecipitation. The association of both proteins was diminished by H2O2. In conclusion, these results suggest that Akt interaction with ASK1 followed by dephosphorylation of the latter is part of the mechanism by which 17β‐estradiol exerts its antiapoptotic action in skeletal muscle cells challenged with stress stimuli.

Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.